BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

OBJECTIVE: To review and summarize the research progress on repairing segmental bone defects using three-dimensional (3D)-printed bone scaffolds combined with vascularized tissue flaps in recent years. METHODS: Relevant literature was reviewed to summarize the application of 3D printing technology in artificial bone scaffolds made from different biomaterials, as well as methods for repairing segmental bone defects by combining these scaffolds with various vascularized tissue flaps. RESULTS: The combination of 3D-printed artificial bone scaffolds with different vascularized tissue flaps has provided new strategies for repairing segmental bone defects. 3D-printed artificial bone scaffolds include 3D-printed polymer scaffolds, bio-ceramic scaffolds, and metal scaffolds. When these scaffolds of different materials are combined with vascularized tissue flaps ( e.g., omental flaps, fascial flaps, periosteal flaps, muscular flaps, and bone flaps), they provide blood supply to the inorganic artificial bone scaffolds. After implantation into the defect site, the scaffolds not only achieve structural filling and mechanical support for the bone defect area, but also promote osteogenesis and vascular regeneration. Additionally, the mechanical properties, porous structure, and biocompatibility of the 3D-printed scaffold materials are key factors influencing their osteogenic efficiency. Furthermore, loading the scaffolds with active components such as osteogenic cells and growth factors can synergistically enhance bone defect healing and vascularization processes. CONCLUSION The repair of segmental bone defects using 3D-printed artificial bone scaffolds combined with vascularized tissue flap transplantation integrates material science technologies with surgical therapeutic approaches, which will significantly improve the clinical treatment outcomes of segmental bone defect repair.
Printing, Three-Dimensional ; Tissue Scaffolds ; Humans ; Surgical Flaps/blood supply* ; Tissue Engineering/methods* ; Plastic Surgery Procedures/methods* ; Bone and Bones/surgery* ; Biocompatible Materials ; Bone Regeneration ; Bone Transplantation/methods* ; Bone Substitutes ; Osteogenesis

OBJECTIVE: To summarize the biomechanical research progress on different fixation methods in medial opening-wedge high tibial osteotomy (MOWHTO) and provide references for selecting appropriate fixation methods in clinical applications of MOWHTO for treating knee osteoarthritis (KOA). METHODS: Recent domestic and international literature on the biomechanical studies of MOWHTO fixation methods was reviewed to analyze the characteristics and biomechanical performance of various fixation techniques. RESULTS: The medial-specific osteotomy plate system has become the mainstream due to its high stiffness and stability, but issues such as soft tissue irritation and stress shielding remain. The use of filler blocks significantly enhances fixation stability and promotes bone healing when the osteotomy gap is large, reducing axial displacement by 73%-76% and decreasing plate stress by 90%. Auxiliary screws improve axial and torsional stability, particularly in cases with large correction angles, effectively preventing lateral hinge fractures. Alternative fixation methods like external fixators hold unique clinical value by minimizing soft tissue irritation and allowing postoperative adjustment. CONCLUSION There is currently no unified standard for selecting MOWHTO fixation methods. Clinical decisions should comprehensively consider factors such as bone quality, correction angle, and postoperative rehabilitation needs.
Humans ; Osteotomy/instrumentation* ; Biomechanical Phenomena ; Tibia/surgery* ; Bone Plates ; Osteoarthritis, Knee/surgery* ; Bone Screws ; External Fixators ; Knee Joint/surgery*

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

Objective The isokinetic muscle strength indicators and surface electromyography(sEMG)signals of the healthy lower limb side of patients with non-contact anterior cruciate ligament(ACL)injury in the acute phase were compared with those of healthy individuals,so to provide a theoretical basis for the prevention of secondary ACL rupture in the healthy lower limb side of patients with ACL injury.Methods 21 patients with ACL injury in the acute phase(ACL injury group)and 21 healthy individuals(control group)were subjected to isokinetic muscle strength tests for hip flexion,extension,adduction,abduction,and knee flexion,and sEMG signals of the vastus medialis,vastus lateralis,semitendinosus,biceps femoris,and gluteus maximus were collected during the single-leg jumping movements.The differences between the two groups in relative peak torque,antagonist muscle ratio,root mean square amplitude,and co-contraction index were analyzed by independent sample t-test.Results The extension of the knee(P=0.040)and hip flexion strength(P=0.041)were lower in the healthy lower limb side of patients with ACL injury.In the single-leg landing action,there were lower activation of the vastus medialis muscle in the pre-activation phase(P=0.014),lower activation of the vastus medialis(P=0.030)and gluteus maximus(P=0.002)in the reaction phase,and also lower co-activation levels of the biceps femoris-semitendinosus(P=0.020).Conclusions At the early stage of injury,the function of the healthy lower limb side of patients with ACL injury changes,which may indicate why these patients face a greater risk of contralateral lower limb injury.

Objective The isokinetic muscle strength indicators and surface electromyography(sEMG)signals of the healthy lower limb side of patients with non-contact anterior cruciate ligament(ACL)injury in the acute phase were compared with those of healthy individuals,so to provide a theoretical basis for the prevention of secondary ACL rupture in the healthy lower limb side of patients with ACL injury.Methods 21 patients with ACL injury in the acute phase(ACL injury group)and 21 healthy individuals(control group)were subjected to isokinetic muscle strength tests for hip flexion,extension,adduction,abduction,and knee flexion,and sEMG signals of the vastus medialis,vastus lateralis,semitendinosus,biceps femoris,and gluteus maximus were collected during the single-leg jumping movements.The differences between the two groups in relative peak torque,antagonist muscle ratio,root mean square amplitude,and co-contraction index were analyzed by independent sample t-test.Results The extension of the knee(P=0.040)and hip flexion strength(P=0.041)were lower in the healthy lower limb side of patients with ACL injury.In the single-leg landing action,there were lower activation of the vastus medialis muscle in the pre-activation phase(P=0.014),lower activation of the vastus medialis(P=0.030)and gluteus maximus(P=0.002)in the reaction phase,and also lower co-activation levels of the biceps femoris-semitendinosus(P=0.020).Conclusions At the early stage of injury,the function of the healthy lower limb side of patients with ACL injury changes,which may indicate why these patients face a greater risk of contralateral lower limb injury.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Objective:To explore the acupoint selection law in acupuncture and moxibustion in treating postpartum incontinence by using data mining technology.Methods:The clinical research literature on acupuncture and moxibustion treatment for postpartum incontinence was retrieved from CNKI, Wanfang Data, VIP, CBM, China Medical Journal Full-text Database, PubMed, Embase, Web of Science from the establishment of the databases to February 1, 2023. The acupoint prescription database was established using Excel 2016 and conducting frequency statistics of acupoints, meridians and specific acupoints. Clustering analysis was performed using SPSS Statistics 25.0, and association rule analysis was performed using SPSS Modeler 18.0.Results:A total of 70 articles were included, involving 70 acupuncture prescriptions and including 31 acupoints with a total frequency of 384 times. The top five acupoints were Sanyinjiao (SP6, 46 times), Guanyuan (CV4, 45 times), Zusanli (ST36, 43 times), Zhongji (RN3, 41 times), and Qihai (CV6, 38 times). The commonly used meridians were Conception Vessel, bladder meridian and spleen meridian. The involved acupoints were mostly located in the lower limbs and belly, and most of them were Jiaohui, Mu and Wushu acupoints. Five effective clustering groups were obtained by clustering analysis of high frequency acupoints. The core acupoint combination of association rules was Sanyinjiao (SP6)-Zusanli (ST36)-Guanyuan (CV4)-Qihai (CV6)-Zhongji (RN3).Conclusions:The pathogenesis of postpartum urinary incontinence is mainly characterized by qi deficiency. Acupuncture and moxibustion treatment of postpartum urinary incontinence follows the principles of invigorating qi and tonifying spleen, nourishing lung and tonifying kidney, paying attention to the use of acupoints in abdomen and lower limbs, and using the methods of upper and lower acupoints, anterior and posterior acupoints.

Objective:To investigate the clinical application of multi-oil fat emulsion (SMOF) in preterm infants with necrotizing enterocolitis (NEC).Methods:Preterm infants with NEC admitted to the Neonatal Intensive Care Unit in our hospital between January 2017 and December 2022 were retrospectively included. According to the type of fat emulsion used, they were divided into SMOF group and medium and long chain triglycerides (MCT/LCT) group. The data of two groups were compared and analyzed.Results:A total of 69 preterm infants were included, 34 in the SMOF group and 35 in the MCT/LCT group. There were no significant differences between the two groups in the levels of total bilirubin, indirect bilirubin, direct bilirubin, bile acid and γ-glutamyl transferase ( P>0.05). There were no significant differences between the two groups in triglyceride, low density lipoprotein and total cholesterol ( P>0.05). There were no significant differences between the two groups in the C reactive protein level, procalcitonin level, and the time to normal C reactive protein ( P>0.05). There were no significant differences in incidence of complications between the two groups, including parenteral nutrition-related cholestasis, bronchopulmonary dysplasia, retinopathy of prematurity, and brain injury ( P>0.05). Conclusions:Compared with MCT/LCT, the application of SMOF did not show significant effect on liver function, inflammation, or incidence of complications (parenteral nutrition-related cholestasis, bronchopulmonary dysplasia and retinopathy of prematurity) in preterm infants with NEC. Multi-center studies with larger sample size are needed for further investigation.

Objective:To screen mutations of the adenosine triphosphate(ATP)-binding cassette transporter A3(ABCA3)gene in elderly Chinese individuals with lung interstitial diseases(ILDs)and to analyze the clinical characteristics of ILDs in elderly patients.Methods:A prospective study, After further image analysis of patients diagnosed with interstitial lung diseases between September 2015 and December 2018 at the Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital of Central South University, 103 patients were willing to provide peripheral blood samples and signed informed consent.DNA samples were extracted and whole exome sequencing was performed to screen ABCA3 gene mutations.Clinical data of patients were summarized and analyzed.Results:Seven rare variants of the ABCA3 gene were identified in 6 patients, with a mean age of 67 years(69-73 years)and an equal sex distribution, and 33.3%(2/6)were smokers.The most notable presentation was diffuse lung lesions.Patients' final diagnoses included idiopathic pulmonary fibrosis(IPF, 3/6), nonspecific interstitial pneumonia(NSIP, 1/6), and IgG4-related lung disease(2/6). Meanwhile, compound heterozygous mutations of the ABCA3 gene responsible for IPF were identified in patient No.39, including p. Asp1465Asn, p.Leu3Vval and p. Val93Ile3, a new finding in patients with ILDs.Conclusions:ABCA3 mutation-related lung interstitial diseases exhibit variable characteristics, with differences in the age of onset, clinical manifestations, imaging features and prognosis between patients.ABCA3 mutations responsible for early-onset ILDs are mostly homozygous or compound heterozygous and usually highly pathogenic nonsense mutations.In contrast, ABCA3 mutations identified in elderly patients with ILDs are often missense mutations, a possible explanation for the variability of ILDs in the elderly.Since patients with ILDs caused by ABCA3 variants respond poorly to currently available treatment options, early genetic diagnosis may benefit patients by enhancing disease awareness.